Soft and pliable absorbable polymers are most often made of block or segmented copolymers consisting of soft amorphous (B) and hard crystalline (A) blocks/segments present in an A-B-A or (A-B)n arrangement. The amorphous component is usually made of flexible chains, and undergoes a glass transition below room temperature. The mobility of the polymer chains in the soft component is accordingly high, and a relatively low mechanical force is required to displace segments of the polymer chains giving rise to the soft characteristics. The crystalline hard components are made of rigid chains and contribute to the overall material physical integrity and final mechanical strength. In various soft tissue applications of sutures, they are preferred to be as soft and pliable as possible to reduce the modulus mismatch between implant and tissue, which can be traumatic and lead to increased inflammatory response. One approach towards achieving this goal is to reduce the copolymer crystallinity and the average size of individual crystallites through using tri- or tetra-functional initiators to result in polyaxial segmented chains. A second approach towards achieving a more compliant suture is to prepare a polyaxial, amorphous initiator and end-graft it with segmented crystallizable components.
Pertinent to the polyaxial approach using a polymeric initiator, U.S. Pat. No. 6,462,169 generally discloses absorbable, crystalline, monocentric, polyaxial copolymers having a crystalline component, and a flexible, amorphous component. The polymers can be prepared from a monomeric initiator, which is a tri- or tetra-functional organic compound, by reacting such initiator with at least one cyclic comonomer, selected from carbonates and lactones to form an amorphous polymeric, polyaxial initiator, and then reacting the amorphous, polymeric, polyaxial initiator with at least one lactone comprising a member selected from the group consisting of glycolide, lactide, p-dioxanone (1,4-dioxan-2-one), and combinations thereof. The copolymers are said to be crystallizable materials with melting temperatures above 100° C., which can be melt-processed into highly compliant absorbable films and fibers. Meanwhile, absorbable fibers made according to the teaching of U.S. Pat. No. 6,462,169 comprised copolymers with high-glycolide-based hard crystallizable components. This limited the respective fibers' or sutures' ability to maintain their mechanical properties in vivo beyond 4 weeks.
Following the successful introduction of polyglycolide (PG, Dexon®, U.S. Surgical Corp., Norwalk, Conn.) and 90/10 poly(glycolide-co-l-lactide (Vicryl®, Ethicon, Somerville, N.J.) as braided sutures, surgeons expressed a strong demand for absorbable, monofilament sutures with longer in vivo breaking strength retention (BSR) profiles and smoother surfaces as compared to their braided counterparts. This led to the development of poly-p-dioxanone (PDS®, Ethicon) and glycolide/trimethylene carbonate block copolymer (Maxon®, Tyco Healthcare), which exhibit BSR of 50 and 30 percent at five weeks, respectively. More recently, there has been a new demand for longer-lasting sutures, which retain more than 50 percent in vivo BSR at 6 to 12 weeks. Accordingly, a 95/5 linear l-lactide/glycolide random copolyester and segmented 88/12 l-lactide/ trimethylene carbonate copolymers were developed into Panacryl® (Ethicon) and Osteoprene® (Poly-Med, Inc., Anderson, S.C.) braided sutures, respectively, and their BSR profiles do meet the aforementioned requirements. However, there exists a strong demand for complaint, absorbable monofilament sutures having an in vivo BSR profile that exceeds that of PDS and preferably being more than 50 percent at 6 to 12 weeks and more preferably at least 50 percent at 6 weeks post-operative. The need for such sutures has become increasingly critical as the demands for repairing compromised tissues increase with the increase in the population of geriatric and diabetic patients. Other particularly important needs for long-lasting monofilament sutures are those associated with musculoskeletal tissue repair and surgical procedures on cancer patients.
The present inventors has now surprisingly found that using lactide as the dominant comonomer for end-grafting onto the amorphous core can lead to a segmented polyaxial copolyester that is well suited for conversion to compliant monofilament sutures with a breaking strength retention (BSR) profile that exceeds any monofilament suture disclosed in the prior art. The inventors were equally surprised to find that copolymerization of l-lactide with a less reactive monomer, such as caprolactone in the presence of a non-crystalline liquid or low melting (50° C. or less) polymeric polyaxial initiator, yields a crystalline, segmented polyaxial copolyester that is suitable for producing compliant monofilament sutures with prolonged in vivo BSR profile.